Leukocyte CD11b Research Articles

Monoclonal Antibody against leucocyte CD11b(MAb 1B6) increase the early mortality rate in Spraque Dawley with E. coli pneumonia

Monoclonal Antibody against leucocyte CD11b(MAb 1B6) increase the early mortality rate in Spraque Dawley with E. coli pneumonia

Radiodetoxified Endotoxin—Induced Tolerance Alters Monocyte but Not Neutrophil CD11b and CD18 Expression in Response to Lipopolysaccharide

To test the hypothesis that pretreatment with radiodetoxified endotoxin (RDE) may mitigate the deleterious effects of subsequent infection, in part by modifying leukocyte adhesion receptor expression, and to investigate the cellular mechanisms of endotoxin tolerance induced by RDE. To assess the effect of RDE pretreatment on mortality from bacterial peritonitis, rats were implanted with an intraperitoneal, barium-fecal inoculum at intervals of 0, 1, 3, and 5 days after RDE injection. Experiments were then conducted to test the effect on leukocyte adhesion receptor expression. Two groups of mice received saline solution, and one group, RDE. After 72 hours, one group received saline solution (saline/saline group), the others, lipopolysaccharide (LPS) (saline/LPS and RDE/LPS groups). Peripheral leukocytes were obtained 1 hour after injection and were analyzed for CD11b and CD18 expression by flow cytometry. Laboratory animal study. Survival rates were not improved in rats that were pretreated with RDE 0 and 24 hours before inoculum (0% and 7%, respectively). In rats that were pretreated 72 hours and 120 hours before inoculum, 47% (P < .01) and 60% (P < .01) survived, respectively. CD18 expression on polymorphonuclear leukocytes increased twofold in the RDE/LPS (mean +/- SEM, 300.3 +/- 32.9) and the saline/LPS (mean +/- SEM, 360.4 +/- 59.9) groups compared with controls (mean +/- SEM, 176.4 +/- 18.9) (P < .05). CD11b expression on polymorphonuclear leukocytes increased threefold in the RDE/LPS (mean +/- SEM, 91.3 +/- 8.1) and the saline/LPS (mean +/- SEM, 89.8 +/- 11.4) groups compared with controls (mean +/- SEM, 32.1 +/- 1.8) (P < .05). CD18 expression on monocytes decreased in the saline/LPS group (mean +/- SEM, 134.2 +/- 14.2) and was unchanged in the RDE/LPS group (mean +/- SEM, 200.2 +/- 17.2) compared with controls (mean +/- SEM, 217.6 +/- 16.5) (P < .05). CD11b expression on monocytes decreased in the saline/LPS group (mean +/- SEM, 25.8 +/- 2.2) and was unchanged in the RDE/LPS group (mean +/- SEM, 36.4 +/- 0.9) compared with controls (mean +/- SEM, 39.7 +/- 3.9) (P < .05). Radiodetoxified endotoxin reduces mortality rates from bacterial peritonitis when given at least 72 hours prior to a bacterial inoculum. Tolerance to subsequent LPS challenge is associated with an abrogation of the reduced peripheral monocyte CD11b and CD18 expression observed in native LPS-stimulated mice but is not associated with changes in polymorphonuclear leukocyte CD11b and CD18 expression. The mechanism of the observed RDE-induced monocyte hyporesponsiveness to LPS and its possible protective effect is uncertain and requires further investigation.

Expression from Leukocyte Integrin Promoters in Retroviral Vectors

Human gene therapy for diseases involving leukocytes would be facilitated by the identification of specific promoter/enhancer sequences capable of directing high levels of tissue and stage-specific expression of the requisite cDNA when used in a retroviral vector. We tested the promoter sequences from the leukocyte integrin CD11a (LFA-1), CD11b (Mac-1), and CD18 subunits in retroviral vectors to express a reporter gene, adenosine deaminase, in the human leukocyte cell lines K562 and HL-60. The leukocyte integrins are expressed in leukocytes, and they are inducible in HL-60 cells, a model system for myeloid differentiation. Although the leukocyte integrin promoter/enhancer sequences direct the expression of reporter genes in myeloid lineage cell lines in transient transfection assays, in these studies, the leukocyte integrin promoters direct low levels of reporter gene expression following retroviral-mediated transduction in K562 and HL-60 cells and selection of stable integrants. Treatment of HL-60 cells transduced with retroviral vectors containing the leukocyte integrin promoters with retinoic acid or phorbol myristate acetate results in less than a two-fold increase in reporter gene expression. These studies indicate that: (i) expression from the leukocyte integrin promoters from stable integrants in retroviral vectors does not parallel the results observed in transient transfection assays, and (ii) additional promoter/enhancer sequences will likely be required for these promoters to direct high levels of tissue and stage-specific expression in retroviral vectors.

Immunological Mapping of the Human Leucocyte Adhesion Glycoprotein gp90 (CD 18) by Monoclonal Antibodies

The leucocyte surface glycoproteins CD11a (gp160, LFA-1 antigen, TA-1 antigen), CD11b (gp155, Mac-1 antigen, OKM1 antigen, Mo-1 antigen), CD11c (gp130, Leu-M5 antigen), and CD18 (gp90) constitute three heterodimers with different alpha chains and a common beta chain. Monoclonal antibodies to CD11a, b, or c block adhesion of certain types of leucocytes only, while several antibodies to CD18 inhibit adhesion in all of them. The functionally important site or sites on CD18 are not known. We have now isolated the CD11a,b,c-CD18 leucocyte antigen complex in large amounts from human leucocytes, and produced several new monoclonal antibodies reacting with CD18. One of these antibodies, like those described earlier, inhibits leucocyte adhesion, whereas the others do not. By means of competition experiments, at least four epitope regions were found. These antibodies should be valuable in elucidating the regions essential in CD18-mediated leucocyte functions.